title: Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine.
abstract: Intravenous (I.V.) cocaine (0.03-3 mg/kg) produced dose-dependent, rapid, and brief increases in blood pressure (BP) in conscious rats pretreated with the dopamine receptor antagonist, SCH 23390. Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, betaCIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced this rapid pressor response, whereas structurally unrelated uptake inhibitors with diverse monoamine transporter selectivities (BTCP, indatraline, GBR 12935, mazindol, nomifensine, and zimeldine) either did not produce a rapid pressor response or produced only a small pressor response. At nonconvulsant doses, the sodium channel blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and tetracaine produced a small pressor response or no increase in BP. In rats implanted with telemetric devices, cocaine and its analog, CFT, produced a biphasic pharmacological response that consisted of an initial brief and abrupt behavioral arousal associated with a rapid, large increase in BP followed by prolonged, parallel increases in BP and locomotor activity. Pretreatment with SCH 23390 prevented the prolonged but not the initial rapid and brief pressor and activity responses to both cocaine and CFT administration. The present data suggest that the inhibition of dopamine, norepinephrine, or serotonin transporter functions, either alone or in combination, does not mediate the rapid pressor response to cocaine. The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid pressor response to cocaine. Finally, the present results confirm previous findings that dopaminergic mechanisms mediate the prolonged increases in BP and locomotor activity produced by cocaine.
authors.affiliation: Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Tella
authors.forename: S R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D013686:Telemetry
chemical_list: D015306:Biogenic Monoamines; D002352:Carrier Proteins; D014179:Neurotransmitter Uptake Inhibitors; D015222:Sodium Channels; D003042:Cocaine